Restoring the balance between disease and repair in multiple sclerosis: insights from mouse models

Abstract

Multiple sclerosis (MS) is considered an autoimmune-mediated demyelinating disease that targets the central nervous system (CNS). Despite considerable research efforts over multiple decades, our understanding of the basic biological processes that are targeted in the disease and the mechanisms of pathogenesis are poorly understood. Consequently, current therapies directed at controlling the progression of the disease are limited in their effectiveness. Historically, the primary focus of MS research has been to define the cellular and molecular basis of the immunological pathogenic mechanisms. Recently, however, it has become clear that long-term functional recovery in MS will require the development of strategies that facilitate myelin repair in lesion areas. The emerging evidence that the adult vertebrate CNS retains the capacity to regenerate neural cells that have been lost to disease or damage has provoked intensive research focused on defining the mechanisms of myelin repair. Unfortunately, the existing animal models of MS are poorly equipped to assess myelin repair, and new validated strategies to identify therapeutics targeted at promoting myelin repair are badly needed. This Commentary will review established murine models of MS, and discuss emerging technologies that promise to provide insights into the mechanisms of myelin repair.

White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study

“…DTI was instrumental in identifying disrupted tissue quality and principal constituents likely affected. Myelin and myelinated axons are amenable to repair with normal aging 27 and white matter diseases 28 . In models of high alcohol exposure, axonal remodeling can occur 29 .…”

Animal models of multiple sclerosis: the good, the bad and the bottom line

“…The model has been used very productively to examine cellular and molecular determinants of remyelination [45][46][47] . The salient strengths of these directly applied toxins lie in isolating demyelination and remyelination as discrete events with spatiotemporal predictability 48 . Their weaknesses inhere in the absence of ongoing immune activity, as seen in MS.…”

Tolerogenic dendritic cells and rheumatoid arthritis: current status and perspectives

“…Recent evidence suggests that steady-state immature DCs, which constitutively present an endogenously expressed antigen, can inactivate fully differentiated memory CD8? T cells in vivo through deletion and inactivation [52]. Moreover, studies have shown that tolDCs that are generated with different immunosuppressive agents and cytokines can induce antigen-specific anergy and regulatory properties in CD4?…”